This project deals with the interactions between EBV-infected cells and the host immune system in normal and immunodefective persons. For an improved understanding of this complex system, it is necessary to broaden our knowledge both on the interaction of the virus with different host cells in vitro and in vivo, and on the interplay between the virally infected cells and the host. This project aims at the analysis of certain questions at both levels, in a mutually interrelated way. The project consists of the following parts: I.Immune responses to EBV and EBV-carrying cells in vitro and in an experimental animal model. II.Virus-cell-host interactions in vivo under normal and pathological conditions. III.Clinically related studies. Part I will deal with the activation of the cellular responses in autologous and allogeneic systems, identification of the EBV-specific rejection targets, experiments to verify or falsify our hypotheses of discriminatory T-cell recognition of different growth transformation associated EBV-proteins, and the study of phenotype dependent differences in B-cell sensitivity to immune rejection. Part II will deal with the presence and expression of EBV genomes in different B-cell subpopulations in vivo, and the evolution of EBV-related malignant epithelial and B-cell phenotypes. Part III will study humoral and cellular responses to virally encoded antigens in healthy seropositives, mononucleosis patients and immunodefectives, viral population exchange in bone marrow transplant patients, EBV-carrying immunoblastic proliferations in immunodefectives, the role of EBV in subfractions of virus carrying chronic lymphocytic leukemia cells, and the role of EBV in nasopharyngeal carcinoma.